Embryonic Microglia Interact with Hypothalamic Radial Glia during Development and Upregulate the TAM Receptors MERTK and AXL following an Insult

Cell Rep. 2021 Jan 5;34(1):108587. doi: 10.1016/j.celrep.2020.108587.


Despite a growing appreciation for microglial influences on the developing brain, the responsiveness of microglia to insults during gestation remains less well characterized, especially in the embryo when microglia themselves are still maturing. Here, we asked if fetal microglia could coordinate an innate immune response to an exogenous insult. Using time-lapse imaging, we showed that hypothalamic microglia actively surveyed their environment by near-constant "touching" of radial glia projections. However, following an insult (i.e., IUE or AAV transduction), this seemingly passive touching became more intimate and long lasting, ultimately resulting in the retraction of radial glial projections and degeneration into small pieces. Mechanistically, the TAM receptors MERTK and AXL were upregulated in microglia following the insult, and Annexin V treatment inhibited radial glia breakage and engulfment by microglia. These data demonstrate a remarkable responsiveness of embryonic microglia to insults during gestation, a critical window for neurodevelopment.

Keywords: embryogenesis; fetal brain; hypothalamus; innate immunity; microglia; radial glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase
  • Brain / embryology
  • Embryo, Mammalian / metabolism*
  • Embryonic Development
  • Ependymoglial Cells / physiology*
  • Gene Expression Regulation, Developmental
  • Hypothalamus / embryology*
  • Hypothalamus / physiology*
  • Immunity, Innate
  • Mice
  • Mice, Transgenic
  • Microglia / physiology*
  • Optical Imaging / methods
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • c-Mer Tyrosine Kinase / metabolism*


  • Proto-Oncogene Proteins
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase
  • Axl Receptor Tyrosine Kinase
  • AXL receptor tyrosine kinase, mouse